The University of California at San Francisco Diabetes Research Center (DRC) functions as a basic and clinical research enterprise at the forefront of diabetes research. The DRC crosses the boundaries of Departments and Schools to support a highly interactive team investigating Type 1 and Type 2 diabetes to advance the understanding and treatment of the disease. The DRC integrates the research activities of the UCSF Diabetes Center, the administrative home of the DRC, with a broader range of diabetes-focused research throughout UCSF. The combined intellectual and research expertise of the DRC encompasses 66 diabetes investigators from 26 departments and organized research units, 3 schools, and six campuses focused on both basic and clinical research, supported with $56,455,025 annual direct costs in diabetes- related grant funding, including $36,070,247 in NIH funding. In this application, we propose to continue the success of the UCSF DRC in promoting, enhancing and integrating diabetes research at UCSF. That goal is realized through support for the following activities: An Administrative Core provides leadership, infrastructure, administrative support, advice and oversight to the other components and members of the DRC, regularly adapts Cores and Programs to fit the needs of the members, and interfaces with the NIDDK, other NIH Diabetes Centers, and the lay community. Biomedical Research Cores: Islet Production Core: Provides mouse and human islets together with expertise, advice and training. Regional Islet Core: Extends the resources of the Islet Core to N. California, Oregon and Washington. Flow Cytometry & Cell Sorting Core: Provides equipment, assistance and training for human and animal cell analysis. Microscopy Core: Provides advanced imaging equipment, technologies, advice and training. Mouse Metabolism Core: Provides the specialized cages, equipment and assistance for mouse metabolic studies. Genetic Modification Core: Provides genome editing, vectors, and transgenic and knock-out mice. A Pilot & Feasibility Program that funds small innovative projects that support new investigators, attract new investigators to diabetes and the DRC, explore new questions by established investigators, promote interactions and lead to external funding support to further the goals of the DRC. An Enrichment Program that supports DRC members and the regional diabetes research community by enhancing scientific exchange and training with seminar series, invited speakers, and an annual retreat.